Purchase this article with an account.
Aihua Jiang, Wenzheng Hu, Hongdi Meng, Hua Gao, Xiaoxi Qiao; Loss of VLDL Receptor Activates Retinal Vascular Endothelial Cells and Promotes Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2009;50(2):844-850. doi: 10.1167/iovs.08-2447.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. The very low-density lipoprotein receptor (VLDLR) knockout (vldlr −/−) mouse has been identified as a model for retinal angiomatous proliferation with subretinal neovascularization (SNV) evolving from retinal vessels. The effects of VLDLR on the angiogenic functions of retinal vascular endothelial cells (RVECs) in vivo and in vitro were examined.
methods. Immunofluorescent staining of markers for activated endothelial cells was performed with CD105 and CD106 antibodies. Proliferation, tube formation, and migration assays were carried out in RVECs isolated from wild-type and vldlr −/− mice to assess the angiogenic functions in vitro. The effect of VLDLR blockage on wild-type RVEC proliferation was also examined.
results. The expression of CD105 and CD106 was significantly upregulated in the retinas of adult vldlr −/− mice, especially at lesion sites. An intense CD105 signal was found in the inner retinas of vldlr −/− mice starting at postnatal day 14, before the onset of SNV. In vitro proliferation assays revealed a significantly enhanced (approximately 20%–100%) growth rate in vldlr −/− RVECs compared with that in the wild-type RVECs. The formation of capillary-like structures in vldlr −/− RVECs was approximately 3 to 11 times greater than in wild-type RVECs. Migration of vldlr −/− RVECs was 1.3 to 3.7 times that of wild-type. VLDLR blockage using a receptor-associated protein or neutralizing anti-VLDLR antibodies significantly enhanced the proliferation rate in wild-type RVECs by more than 200% and 30%, respectively.
conclusions. VLDLR is a potent endogenous inhibitor that negatively regulates the angiogenic properties of RVECs. Loss of VLDLR activates RVECs and significantly enhances angiogenesis in vivo and in vitro.
This PDF is available to Subscribers Only